E3106-18 基于科学和风险的清洁工艺开发和验证的标准指南

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逛论坛无意间看到这份指南，在此帖连载一下翻译好了下载地址：https://www.ouryao.com/thread-467377-1-1.html

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@野性之吻 已上传中英版

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目录：
1.SCOPE 范围
2.Reference Documents参考文献
3.Terminology 术语
4.Significance and use 意义和用途
5.Science-Based, Risk-Based, and Statistics-Based Cleaning Process Development and Validation 基于科学、风险、数据的清洁工艺开发和验证
6.Risk assessment 风险评估
7.Risk control 风险控制
8.Risk review 风险回顾
9.Risk communication 风险交流
10.keywords 关键词

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1.SCOPE 范围
1.1 This guide applies the life-cycle approach to cleaning process validation, which includes the development, qualification, and verification of cleaning processes. It is applicable to pharmaceuticals (including active pharmaceutical ingredients (APIs); dosage forms;and over-the-counter, veterinary, biologics, and clinical supplies) and is also appli- cable to other health, cosmetics, and consumer products.
此指南将生命周期方法应用于清洁工艺验证（包括清洁工艺方法开发、确认、验证）。它将适用于多种类型药物（包括API、剂型、OTC、兽用药、生物药、临床用药），并且适用于其他保健品、化妆品和消费品。
1.2 This guide is focused only on the cleaning of equipment product contact surfaces and does not cover disinfection or non-product contact surfaces (which are covered under other existing guides: Ref (1),2 USP <1072>, Guide E2614, and ISO 14698).
此指南仅关注设备与产品接触面的清洁，不包括设备消毒或不与产品接触的表面（此部分指导见其他指南：USP<1072>,指南E2614,ISO14698）。
1.3 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.
本指南使用SI单位作为标准单位。除此之外指南内未使用其他计量单位。
1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and deter- mine the applicability of regulatory limitations prior to use.
标准指南的目的并不是解决与使用相关的所有安全问题(如果有的话)。本标准的使用者有责任在使用前建立适当的安全、健康和环境规范，并确定法规限制的适用性。
1.5 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.（不翻了，是介绍此标准基于啥啥啥发展起来）

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2. Reference documents 参考文献（略）
3.Terminology 术语（略）
4.Significance and Use 意义和用途（略）
5.Science-Based, Risk-Based, and Statistics-Based Cleaning Process Development and Validation 基于科学、风险、数据的清洁工艺开发和验证
5.1 Science-based approaches should be applied throughout the cleaning process development and validation process.
     基于科学的方法应应用于清洁工艺的整个开发和验证过程。
5.2 Quality risk management should be applied throughout the cleaning process development and validation process.
       质量风险管理应贯穿于清洁工艺开发和验证过程。
5.3 Appropriate statistical analysis should be applied throughout the cleaning process development and validation process.
    相应的数据分析应贯穿清洁工艺开发和验证过程。

野性之吻

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野性之吻

赖颖 发表于 2019-1-31 14:28
2. Reference documents 参考文献（略）
3.Terminology 术语（略）
4.Significance and Use 意义和用途（ ...

求一份 中英文  

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6.Risk Assessment 风险评估
6.1 Under ICH Q9, risk assessment is broken into three stages: risk identification, risk analysis, and risk evaluation.
    基于ICH Q9，风险评估可分为三个阶段：风险识别，风险分析，风险评估
6.2 Risk can be defined as: risk = f (probability of occurrence of harm and the severity of that harm).
    风险可以被定义为：风险=f（发生的可能性及损害的严重程度)
6.3 For the purposes of cleaning, risk can be further defined as a function of the severity of the hazards of process residues,likelihood and level of process residues, and detectability of process residues.
对于清洁来说，风险可以进一步定义为工艺残留危害的严重程度、工艺残留的可能性和级别以及工艺残留物的可检测性三者之间的函数。
6.4 For a reliable assessment of risk, scientific means (for example, risk management tools) should be used to identify the hazard presented by a process residue (for example, API, degradation products, intermediates, cleaning agent, bioburden/endotoxin, and so forth), the ability of a cleaning process to remove process residues to levels that are acceptable, and the ability to detect and quantify the presence of process residues after cleaning.
   对于一个可靠的风险评估，科学手段（例如，风险管理工具）应当用于识别工艺残留风险（例如，API、产品分解物、中间体、清洁剂、生物负载/内毒素等等）、将过程残留物清除到可接受水平的能力、清洗后检测和量化工艺残留物的能力。
6.5 Risk Identification—Risk identification should encompass the identification of process residue hazards, equipment design hazards, and procedural hazards.
    风险识别-风险识别应包含工艺残留风险、设备设计风险和程序风险的识别。
6.5.1 Process Residue Hazard Identification 工艺残留风险识别:
6.5.1.1 The hazard presented by a potential process residue may be determined from a toxicological review performed by a qualified toxicologist or qualified pharmacologist. 一个潜在的工艺残留物的危害可以由一个有资质的毒理学家或合格的药理学家进行毒理学检查来确定。For an API, this involves a thorough review of all relevant toxicologi- cal data available for the process residue under study (9). When preclinical and clinical data on APIs are available to review, an ADE can be determined and used as a measure of the severity of hazard presented by a compound. For further information,see the ISPE Risk-MaPP Guide (1) or the EMA Guideline on Setting Health Based Exposure Limits for Use in Risk Identi- fication in the Manufacture of Different Medicinal Products in Shared Facilities Guideline on Setting Health Based Exposure Limits for Use in Risk Identification in the Manufacture of Different Medicinal Products in Shared Facilities.
对于原料药来说，这需要对研究中残留的所有相关毒理学数据进行彻底的审查(9)。当有关于原料药的临床前和临床数据可供审查时，就可以确定ADE，并将其作为衡量化合物危害程度的指标。有关更多信息，请参见ISPE Risk-MaPP指南(1)或EMA指南：在共用设施中生产不同药品的风险识别和设置基于健康的暴露限值。
6.5.1.2 When an ADE is not available, such as for intermediates, degradation products, or compounds in early development, alternative approaches such as the threshold of toxicological concern (TTC) may be justified (9, 10).Although compounds in early development may not have sufficient safety data to perform a complete analysis, useful information can be found in the chemical structure of a compound to help determine a provisional ADE for the compound.  “In silico” (computer-assisted) toxicological assessment or a structure activity relationship can be used to determine provisional ADEs for a compound (11, 12).For example, a compound in the same structural series of a known API from a given therapeutic class can be treated in the same way as that API,for example, a compound with a propylamine structure would be expected to share properties of this class of antihistamines.Where data are available on comparative potency, these can be used to adjust the estimated ADE.
当ADE值无法获取，例如中间体、产品分解物、或处于早期开发研究阶段的化合物，可用替代方法，例如毒理学阈值（TTC）可能是可行的。虽然早期开发的化合物可能没有足够的数据来执行完整的分析，但在化合物的化学结构中可以找到有用的信息，以帮助确定化合物的假定ADE。“In silico”(计算机辅助)毒理学评估或结构活性关系可用于确定化合物的ADE(11,12)。例如，与特定治疗类的已知原料药具有相同结构序列的化合物可以采用与该原料药相同的方法进行治疗。例如，一种具有丙胺结构的化合物可能具有这类抗组胺药物的共同特性。如果有关于比较药效的数据，这些数据可用于调整估计的ADE。
6.5.1.3 The hazard of possible bioburden from a previous product and the possibility of microbial proliferation after a cleaning process and the hazards this presents,including the need for subsequent disinfection, should also be considered.For example, the hazard(s) presented by holding equipment either in a dirty state or in clean state should be considered or the possibility of endotoxin and the need for subsequent depyrogenation should be considered.
还应考虑前一生产产品中可能产生的生物污染的风险以及清洗过程后微生物增殖的可能性及其带来的风险，以及是否需要进行随后的消毒。例如，应考虑保持设备处于未清洁状态或清洁后状态所带来的风险，或者应该考虑内毒素的可能性以及随后脱硫的必要性。
6.5.2 Equipment Hazard Identification—The potential hazards presented by equipment design should also be considered,such as the possibility of product buildup. Equipment should be designed to facilitate cleaning, inspection, and monitoring.
设备风险识别—应考虑设备设计中可能出现的风险，比如产品残留的可能性。设备的设计应便于清洗、检查和监视。
6.5.3 Procedural Hazard Identification—Before use, cleaning procedures should be subjected to risk assessments,for example, cleaning FMEA or other risk management tools, to minimize risk of failure (for example, to ensure that product buildup is avoided),improve the cleaning procedures, and make the cleaning procedures more reliable and robust.
清洁方案风险评估—在使用前，清洁方案应进行风险评估，例如，清洁FMEA评估或其他风险管理工具，以减少失败的风险（例如，确保避免产品积聚），完善清洁方案，使清洁方案更加可靠、稳健。

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6.6 Risk analysis 风险分析
6.6.1 After identifying the hazards posed, the risks associ- ated with them should be analyzed. This risk analysis should involve the cleaning process development, facility/equipment design review, cleaning procedure review, and the selection of analytical methods.The analysis should also determine what steps can be taken to mitigate the identified risks.
   在确定所构成的危害之后，应当分析与之相伴随的风险。这种风险分析应该包括清洁过程的开发，设备设计回顾，清洁方案回顾，分析方法的选择。分析还应该确定可以采取哪些步骤来减轻所识别出的风险。
6.6.2 The risk analysis should show how cleaning may affect the patient safety and quality of the next product.
       风险分析应表明清洁如何影响患者的安全和下一生产产品的质量。
6.6.3 The impact of the different factors (process residue, cleaning/rinsing agents, equipment engineering, and so forth) on the outcome of the cleaning process should be analyzed.
      应分析不同因素(工艺残留、清洗/漂洗剂、设备工程等)对清洁工艺结果的影响。
6.6.4 The cleaning process risk analysis can help to determine the necessary cleaning qualifications and identify appropriate
      risk control mechanisms.
      清洁工艺风险分析可以帮助识别出会必需的清洁效果确认和确定适当的风险控制机制。
6.6.5 Process Residue Characterization 工艺残留特性
6.6.5.1 The chemistry of process residues should be understood to design an effective and efficient cleaning cycle,for example, cleanability of process residues (for example, highly insoluble or strongly adhesive residues) and potential interactions (for example, staining, corrosion) of process residues with equipment.
        为了设计一个高效的清洁循环，必须充分的认识工艺残留化学成分，如工艺残留物的可清洗性(如高不溶性或强粘附性残留物)以及过程残留物与设备之间潜在的相互作用(例如，染色、腐蚀)。
6.6.5.2 The chemistry and potential interactions between process residues and chemicals used as part of cleaning processes should also be understood, for example, the solubility of process residues in cleaning agents or rinsing agents should be considered, to avoid situations in which process residues are not removed or whether degradation products may be formed  that may be harder to clean or more toxic than the original process residue.
还应了解工艺残留与作为清洗过程一部分的化学品之间的潜在化学相互作用，例如，应考虑清洗剂或漂洗剂中工艺残留物的溶解度，避免工艺残留物未被清除或可能形成比原工艺残留物更难清洁或毒性更大的降解产物的情况。

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6.6.6 Equipment Design for Cleanability 洁净性设备设计
6.6.6.1 The design of equipment has an impact on its cleanability. Equipment design should be considered as part of the risk analysis taking into consideration the likely type of cleaning process that will be applied to that equipment.The variables and attributes related to equipment design should be identified and linked to the cleaning critical attributes using the appropriate risk assessment tool(s). Examples of equipment design considerations may include: materials of construction, presence of dead legs or other areas in which material could become trapped, or drainability.
设备的设计对其清洁度有影响。设备设计应作为风险分析的一部分，考虑可能应用于该设备的清洁类型。应确定与设备设计有关的变量和属性，并使用适当的风险评估工具将其与清洁关键属性联系起来。设备设计考虑因素的例子可包括:结构材料、存在死角或其他可能积聚物料的区域。以及排水能力。
6.6.7 Evaluation of Historical Cleaning Data—The history of cleanings (along with any deviations, investigations, and corrective actions) should be reviewed. This cleaning process understanding and knowledge can provide useful information in a risk analysis and may help identify cleaning process parameters to be used in cleaning process development studies and determine the likelihood of a cleaning failure (ICH Q10)
历史清洗数据的评估- - -清洁的历史(以及任何偏差、调查和纠正措施)应予以回顾。对这种清洁工艺的理解和知识可以为风险分析提供有用的信息，并可帮助确定清洁工艺参数，以用于清洁工艺开发研究，以及确定清洁故障的可能性。（ICH Q10）

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基于科学和风险的清洁工艺开发和验证的标准指南 [

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野性之吻

赖颖 发表于 2019-2-20 10:02
@野性之吻 已上传中英版

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康红 发表于 2019-2-25 09:19
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